1. Blood Ch 19 Blood and Hemostasis Muse Lecture #1 Bio 2440 5/8/12

2. Introduction to the Cardiovascular System  A circulating transport system  A pump (the heart)  A conducting system (blood vessels)  A fluid medium (blood)  Is specialized fluid of connective tissue  Contains cells suspended in a fluid matrix

3. Introduction to the Cardiovascular System  To transport materials to and from cells  Oxygen and carbon dioxide  Nutrients  Hormones  Immune system components  Waste products

4. Functions of Blood  Transport of dissolved substances  Regulation of pH and ions  Restriction of fluid losses at injury sites  Defense against toxins and pathogens  Stabilization of body temperature

5. Physical Characteristics of Blood  Whole Blood  Plasma  Fluid consisting of: –water –dissolved plasma proteins (albumins and globulins) –other solutes (salt, dissolved gasses)  Formed elements  All cells and solids

6. Physical Characteristics of Blood Figure 19–1 The Composition of Whole Blood

7. Physical Characteristics of Blood Figure 19–1b The Composition of a Typical Sample of Plasma

8. Physical Characteristics of Blood Figure 19–1c The Composition of Formed Elements of Blood

9. Physical Characteristics of Blood  Three Types of Formed Elements  Red blood cells (RBCs) or erythrocytes  Transport oxygen - red because of hemoglobin  White blood cells (WBCs) or leukocytes  Part of the immune system  Platelets  Cell fragments involved in clotting

10. Physical Characteristics of Blood  Hemopoiesis  Process of producing formed elements  By myeloid and lymphoid stem cells  Fractionation  Process of separating whole blood for clinical analysis  Into plasma and formed elements centrifugation or filtering

11. Physical Characteristics of Blood  Three General Characteristics of Blood  38°C (100.4°F) is normal temperature  High viscosity  Slightly alkaline pH (7.35–7.45)

12. Physical Characteristics of Blood  Blood volume (liters) = 7% of body weight (kilograms)  Adult male: 5 to 6 liters  Adult female: 4 to 5 liters

13. Plasma  Makes up 50–60% of blood volume  More than 90% of plasma is water  Extracellular fluids  Interstitial fluid (IF) and plasma  Materials plasma and IF exchange across capillary walls  Water  Ions  Small solutes

14. Plasma  Differences between Plasma and IF  Levels of O 2 and CO 2  Concentrations and types of dissolved proteins  Plasma proteins do not pass through capillary walls

15. Plasma  Plasma Proteins  Albumins (60%)  Transport substances such as fatty acids, thyroid hormones, and steroid hormones. HSA- Human Serum Albumin is also a redox buffer to protect proteins from oxidation.  Globulins (35%)  Antibodies, also called immunoglobulins  Transport globulins (small molecules): hormone-binding proteins, metalloproteins, apolipoproteins (lipoproteins), and steroid-binding proteins  Fibrinogen (4%)  Molecules that form clots and produce long, insoluble strands of fibrin

16. Plasma  Serum  Liquid part of a blood sample  In which dissolved fibrinogen has converted to solid fibrin  Other Plasma Proteins  1% of plasma  Changing quantities of specialized plasma proteins  Enzymes, hormones, and prohormones

17. Plasma  Origins of Plasma Proteins  90% + made in liver  Antibodies made by plasma cells ( WBC s( B-cells )  Peptide hormones made by endocrine organs

18. Red Blood Cells  Red blood cells (RBCs) make up 99.9% of blood’s formed elements  Hemoglobin  The red pigment that gives whole blood its color  Binds and transports both oxygen and carbon dioxide

19. Red Blood Cells  Abundance of RBCs  Red blood cell count: the number of RBCs in 1 microliter of whole blood  Male: 4.5–6.3 million  Female: 4.2–5.5 million  Hematocrit (packed cell volume, PCV): percentage of RBCs in centrifuged whole blood  Male: 40–54  Female: 37–47

20. Red Blood Cells  Structure of RBCs - anucleate in mammals  Small and highly specialized discs  Thin in middle and thicker at edge  Importance of RBC Shape and Size  High surface-to-volume ratio  Quickly absorbs and releases oxygen  Discs form stacks called rouleaux  Smooth the flow through narrow blood vessels  Discs bend and flex entering small capillaries:  7.8 µm RBC passes through 4 µm capillary Figure 19–2d

21. Red Blood Cells Figure 19–2a–c The Anatomy of Red Blood Cells

22. Red Blood Cells Figure 19–2d The Anatomy of Red Blood Cells

23. Red Blood Cells  Lifespan of RBCs  Lack nuclei, mitochondria, and ribosomes  Means no repair and anaerobic metabolism  Live about 120 days

24. Red Blood Cells  Hemoglobin (Hb)  Protein molecule, that transports respiratory gases  Normal hemoglobin (adult male)  14–18 g/dL whole blood  Normal hemoglobin (adult female)  12–16 g/dL, whole blood

25. Red Blood Cells  Hemoglobin Structure  Complex quaternary structure  Four globular protein subunits:  Each with one molecule of heme  Each heme contains one iron ion  Iron ions  Associate easily with oxygen (oxyhemoglobin) »OR  Dissociate easily from oxygen (deoxyhemoglobin) Figure 19–3

26. Red Blood Cells Figure 19–3 The Structure of Hemoglobin

27. Figure 17.4 Heme group (a) Hemoglobin consists of globin (two alpha and two beta polypeptide chains) and four heme groups. (b) Iron-containing heme pigment.  Globin chains  Globin chains

28. Red Blood Cells  Fetal Hemoglobin  Strong form of hemoglobin found in embryos  Takes oxygen from mother’s hemoglobin

29. Red Blood Cells  Hemoglobin Function  Carries oxygen  With low oxygen (peripheral capillaries)  Hemoglobin releases oxygen  Binds carbon dioxide and carries it to lungs –Forms carbaminohemoglobin

30. Red Blood Cells Figure 19–4 ”Sickling” in Red Blood Cells B-globin D6V

31. Red Blood Cells  RBC Formation and Turnover  1% of circulating RBCs wear out per day  About 3 million RBCs per second  Macrophages of liver, spleen, and bone marrow  Monitor RBCs  Engulf RBCs before membranes rupture (hemolyze)

32. Red Blood Cells  Hemoglobin Conversion and Recycling  Phagocytes break hemoglobin into components  Globular proteins to amino acids  Heme to biliverdin  Iron  Hemoglobinuria  Hemoglobin breakdown products in urine due to excess hemolysis in bloodstream  Hematuria  Whole red blood cells in urine due to kidney or tissue damage

33. Red Blood Cells  Iron Recycling  Iron removed from heme leaving biliverdin  To transport proteins (transferrin)  To storage proteins (ferritin and hemosiderin)

34. Red Blood Cells  Breakdown of Biliverdin  Biliverdin (green) is converted to bilirubin (yellow)  Bilirubin is: –excreted by liver (bile) –jaundice is caused by bilirubin buildup –converted by intestinal bacteria to urobilins and stercobilins

35. Red Blood Cells Figure 19–5 Recycling of Red Blood Cell Components

36. Red Blood Cells  RBC Production  Erythropoiesis  Occurs only in myeloid tissue (red bone marrow) in adults  Stem cells mature to become RBCs  Hemocytoblasts  Stem cells in myeloid tissue divide to produce  Myeloid stem cells: become RBCs, some WBCs  Lymphoid stem cells: become lymphocytes

37. Red Blood Cells  Stages of RBC Maturation  Myeloid stem cell  Proerythroblast  Erythroblasts  Reticulocyte  Mature RBC

38. Red Blood Cells Figure 19–6 Stages of RBC Maturation

39. Figure 17.5 Stem cell Hemocytoblast Proerythro- blast Early erythroblast Late erythroblast Normoblast Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus Reticulo- cyte Erythro- cyte Committed cell Developmental pathway Enters blood stream

40. Red Blood Cells  Regulation of Erythropoiesis  Building red blood cells requires  Amino acids  Iron  Vitamins B 12, B 6, and folic acid: –pernicious anemia »low RBC production »due to unavailability of vitamin B 12

41. Figure 17.6 Kidney (and liver to a smaller extent) releases erythropoietin. Erythropoietin stimulates red bone marrow. Enhanced erythropoiesis increases RBC count. O 2 - carrying ability of blood increases. Homeostasis: Normal blood oxygen levels Stimulus: Hypoxia (low blood O 2 - carrying ability) due to Decreased RBC count Decreased amount of hemoglobin Decreased availability of O 2 1 2 3 4 5 IMBALANCE This is why athletes train in low altitude

42. Red Blood Cells

43.  Stimulating Hormones  Erythropoietin (EPO)  Also called erythropoiesis-stimulating hormone  Secreted when oxygen in peripheral tissues is low (hypoxia)  Due to disease or high altitude

44. Blood Typing  Are cell surface proteins that identify cells to immune system  Normal cells are ignored and foreign cells attacked  Blood types  Are genetically determined  By presence or absence of RBC surface antigens A, B, Rh (or D)

45. Blood Typing  Four Basic Blood Types  A (surface antigen A)  B (surface antigen B)  AB (antigens A and B)  O (neither A nor B) Landsteiner

46. Blood Typing Figure 19–7a Blood Types and Cross-Reactions

47. Blood Typing  Agglutinogens  Antigens on surface of RBCs  Screened by immune system  Plasma antibodies attack and agglutinate (clump) foreign antigens

48. Blood Typing  Blood Plasma Antibodies  Type A person  Type B antibodies in sera  Type B  Type A antibodies in sera  Type O  Both A and B antibodies in sera  Type AB  Neither A nor B antibodies in sera

49. Blood Typing  The Rh Factor  Also called D antigen  Either Rh positive (Rh + ) or Rh negative (Rh - )  Only sensitized Rh - blood has anti-Rh antibodies

50. Blood Typing Figure 19–9 Rh Factors and Pregnancy

51. Blood Typing  RhoGAM Figure 19–9 Rh Factors and Pregnancy Can be used to chelate

52. Blood Typing  Cross-Reactions in Transfusions  Also called transfusion reaction  Plasma antibody meets its specific surface antigen  Blood will agglutinate and hemolyze  Occur if donor and recipient blood types not compatible

53. Blood Typing Figure 19–7b Blood Types and Cross-Reactions

54. Blood Typing  Cross-Match Testing for Transfusion Compatibility  Performed on donor and recipient blood for compatibility  Without cross-match, type O - is universal donor

55. Blood Typing Figure 19–8 Blood Type Testing

56. ABO Blood Typing

57. Blood Typing

58. Figure 17.9 Formed elements Platelets Leukocytes Erythrocytes Differential WBC count (All total 4800 – 10,800/l) Neutrophils (50 – 70%) Lymphocytes (25 – 45%) Eosinophils (2 – 4%) Basophils (0.5 – 1%) Monocytes (3 – 8%) Agranulocytes Granulocytes

59. White Blood Cells Figure 19–11 The Origins and Differentiation of Formed Elements

60. Platelets  Cell fragments involved in human clotting system  Nonmammalian vertebrates have thrombocytes (nucleated cells)  Circulate for 9–12 days  Are removed by spleen  2/3 are reserved for emergencies

61. Platelets  Platelet Counts  150,000 to 500,000 per microliter  Thrombocytopenia  Abnormally low platelet count  Thrombocytosis  Abnormally high platelet count

62. Platelets  Three Functions of Platelets: 1.Release important clotting chemicals 2.Temporarily patch damaged vessel walls 3.Actively contract tissue after clot formation

63. Platelets  Platelet Production  Also called thrombocytopoiesis  Occurs in bone marrow  Megakaryocytes  Giant cells in bone marrow  Manufacture platelets from cytoplasm

64. Platelets  Platelet Production  Hormonal controls  Thrombopoietin (TPO)  Interleukin-6 (IL-6)  Multi-CSF

65. Hemostasis  Hemostasis is the cessation of bleeding  Consists of three phases  Vascular phase  Platelet phase  Coagulation phase

66. Hemostasis  The Vascular Phase  A cut triggers vascular spasm that lasts 30 minutes  Three steps of the vascular phase  Endothelial cells contract: –expose basal lamina to bloodstream  Endothelial cells release: –chemical factors: ADP, tissue factor, and prostacyclin –local hormones: endothelins –stimulate smooth muscle contraction and cell division  Endothelial plasma membranes become “sticky”: –seal off blood flow

67. Hemostasis  The Platelet Phase  Begins within 15 seconds after injury  Platelet adhesion (attachment)  To sticky endothelial surfaces  To basal laminae  To exposed collagen fibers  Platelet aggregation (stick together)  Forms platelet plug  Closes small breaks Figure 19–11b

68. Hemostasis  Platelet Phase  Activated platelets release clotting compounds  Adenosine diphosphate (ADP)  Thromboxane A 2 and serotonin  Clotting factors  Platelet-derived growth factor (PDGF)  Calcium ions

69. Hemostasis  Factors that limit the growth of the platelet plug  Prostacyclin, released by endothelial cells, inhibits platelet aggregation  Inhibitory compounds released by other white blood cells  Circulating enzymes break down ADP  Negative (inhibitory) feedback: from serotonin  Development of blood clot isolates area

70. Hemostasis Figure 19–12 The Vascular and Platelet Phases of Hemostasis.

71. Hemostasis  The Coagulation Phase  Begins 30 seconds or more after the injury  Blood clotting (coagulation)  Cascade reactions: –chain reactions of enzymes and proenzymes –form three pathways –convert circulating fibrinogen into insoluble fibrin Figure 19–12a

72. Hemostasis  Clotting Factors  Also called procoagulants  Proteins or ions in plasma  Required for normal clotting

73. Hemostasis Hemophelia is a loss of any one of these

74. Hemostasis  Three Coagulation Pathways  Extrinsic pathway  Begins in the vessel wall  Outside bloodstream  Intrinsic pathway  Begins with circulating proenzymes  Within bloodstream  Common pathway  Where intrinsic and extrinsic pathways converge

75. Hemostasis  The Extrinsic Pathway  Damaged cells release tissue factor (TF)  TF + other compounds = enzyme complex  Activates Factor X

76. Hemostasis  The Intrinsic Pathway  Activation of enzymes by collagen  Platelets release factors (e.g., PF–3)  Series of reactions activates Factor X

77. Figure 17.14 (1 of 2) Vessel endothelium ruptures, exposing underlying tissues (e.g., collagen) PF 3 released by aggregated platelets XII XI IX XII a Ca 2+ XI a IX a Intrinsic pathway Phase 1 Tissue cell trauma exposes blood to Platelets cling and their surfaces provide sites for mobilization of factors Extrinsic pathway Tissue factor (TF) VII VII a VIII VIII a Ca 2+ X XaXa Prothrombin activator PF 3 TF/VII a complex IXa/VIII a complex V VaVa

78. Hemostasis  The Common Pathway  Forms enzyme prothrombinase  Converts prothrombin to thrombin  Thrombin converts fibrinogen to fibrin

79. Hemostasis  Stimulates formation of tissue factor  Stimulates release of PF-3  Forms positive feedback loop (intrinsic and extrinsic)  Accelerates clotting

80. Hemostasis Figure 19–13a The Coagulation Phase of Hemostasis

81. Hemostasis Figure 19–13b The Coagulation Phase of Hemostasis

83. 3 Stages of Clotting  Extrinsic or intrinsic pathways lead to formation of prothrombinase  Prothrombinase converts prothrombin into thrombin  Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot

84. Hemostasis  Clotting: Area Restriction  Anticoagulants (plasma proteins)  Antithrombin-III  Alpha-2-macroglobulin  Heparin  Protein C (activated by thrombomodulin)  Prostacyclin  hirudin (leech protein)  EDTA

85. Hemostasis  Calcium Ions, Vitamin K, and Blood Clotting  Calcium ions (Ca 2+ ) and vitamin K are both essential to the clotting process

86. Hemostasis  Clot Retraction  After clot has formed  Platelets contract and pull torn area together  Takes 30–60 minutes

87. Hemostasis  Fibrinolysis  Slow process of dissolving clot  Thrombin and tissue plasminogen activator (t-PA): –activate plasminogen  Plasminogen produces plasmin  Digests fibrin strands TPA to treat strokes

88. I shuued haf studied harder for my A & P exam